Anoxia inhibits guanosine salvage in cardiac myocytes.
The adult heart depends largely on salvage synthesis to supply its 5'-nucleotide needs. Previous work from this laboratory established that guanosine is metabolized into guanine 5'-nucleotides in heart cells, but that salvage rates are very slow as compared to adenosine. The author hypothesized that guanosine salvage is regulated according to the needs of the cell for guanine nucleotides. This hypothesis was tested using cardiac myocytes which were rendered anoxic for 0-60 min. During this anoxic period, guanine nucleotides were depleted about 50%. At 0, 30, and 60 min, aliquots were removed for cell counting and nucleotide analysis; 50 microM 3H-guanosine was then added and the incubation continued for 1 min. The cells were then extracted and assayed for radioactivity in the guanine nucleotide products. Anoxia for 60 min, depressed GTP levels by 89%, total guanine nucleotides by 50%, and short-term guanosine salvage by 48% over aerobic controls. Reoxygenation of the myocytes after 30 min of anoxia returned guanosine salvage rates to nearly normal (87% of control). Preincubation of the myocytes with 5 mM ribose for times up to 1 hour modestly increased salvage rates of guanosine in aerobic cells. These results suggest that guanosine salvage in cardiac myocytes is not regulated by the size of the guanine nucleotide pool (that is, not sensitive to the demand for guanine nucleotides). Instead, salvage of guanosine is probably limited by cytosolic levels of ATP or phosphoribosylpyrophosphate, the production of which are dependent on adequate oxygen supplies.
Geisbuhler
T P
TP
Kirksville College of Osteopathic Medicine, Department of Physiology, MO 63501, USA.
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D006150:Guanine Nucleotides / Q000378:metabolism; D006151:Guanosine / Q000096:biosynthesis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats
D006150:Guanine Nucleotides; D006151:Guanosine